Michael Blaese's laboratory continues to focus on the development of gene therapy. On 9/14/90, his group performed the first authorized use of gene transfer to treat human disease when they infused 10(9) autologous ADA gene-corrected T cells into a 4-yr-old girl with ADA deficiency SCID. Retroviral-mediated gene transfer was used to insert a normal human ADA gene into this girl's polyclonal peripheral blood T cells which had been stimulated in tissue culture with an anti-T cell receptor monoclonal antibody and IL2. The gene-corrected T cells were expanded 100-1000 fold and then returned iv within 2 weeks to maintain a polyclonal repertoire. This girl and a second ADA deficiency patient have been treated every 5-7 weeks with such gene-corrected T cell infusions and are now each showing signs of reconstituted immune reactivity. Each child now has a normal peripheral blood T cell count and each has begun to produce normal amounts of isohemagglutinins in response to environmental antigenic stimulation. The first child has a positive, delated hypersensitivity response to tetanus toxoid for the first time in her life. Extensive data on the quality of immune system function and the duration of the gene transfer effect are continuing to be collected and analyzed on these patients. Similar cellular immunoreconstitution protocols are being developed to treat patients AIDS in the coming year. In addition to our ongoing clinical and laboratory evaluation of other immunodeficiency disorders such as the Wiskott-Aldrich syndrome, work has also continued on the development of succinylacetone (SA) as a clinically useful immunosuppressive effects in rats, mice, dogs, miniature swine and non- human primates. It is effective in preventing allograft rejection, graft vs host disease, antibody production in these experimental animal models and has shown utility in treating several different autoimmune disorders including experimental autoimmune uveitis and adjuvant arthritis.